Lecture 3 - Effector Immune functions Flashcards
What are the 5 different types of constant regions (Fc) of the heavy chain?
IgM IgD IgE IgG IgA
What is the purpose of having different types of constant region of the heavy chain?
- lead to different antibody structure and function
- different types found in different areas of the body as have different function
What is the structure and function of the IgG Fc region?
- occurs as a dimer of 2 heavy chains and 2 light chains
- high affinity antibody with a key role in memory immune responses (protect against viruses and toxins)
- most common immunoglobulin in serum
What is the concentration of different types of antibody following vaccination?
1) IgM peaks at low levels with affinity not changing much over time
2) As immune system continues response, IgG affinity increases -> increasingly higher levels of IgG with increasing affinity
What is the structure of IgM?
pentameric structure with 5 antibody dimers held together by J chain protein
What is the features of IgM?
- low affinity antibody with role in protection during immune response
- first antibody made during an immune response
- makes up for low affinity by having 10 binding sites
- becomes an IgG molecule as a result of AID in somatic hypermutation
What is the structure of IgA?
dimeric structure with 2 antibody dimers held together by J chain protein
What are the features of IgA?
- found in mucosal secretions as can cross mucosal surfaces e.g. into intestine
- lymph node and pyrus patch produce B cells producing IgA -> transported into gut lumen through epithelial cells at base of crypts -> dimeric IgA binds to layer of gut mucus overlaying epithelium -> binds to pathogens + neutralises
- found in breastmilk -> into baby gut and intestines when born and suddenly into contact with bacteria mother already encountered has some protection, into bloodstream
What is the structure of IgE?
similar to IgG, a dimer of two heavy chains and light chains but with a difference in the ‘tail’
What are the features of IgE?
- crosslinks to special receptors on mast cells and eosinophils, when bound, release histodine
- role in allergic responses
Why is IgM made first?
normally transcription will through through, after VJD rearrangments, into Cu (IgM) and THEN C& (IgG)
How does class switching occur to produce IgG instead of IgM?
1) AID is only expressed in cells undergoing somatic hypermutation
2) AID induces breaks above Cu (Su and S&1 switch regions)
3) Body goes in to repair DNA, causing reciprocal breaks to occur
4) dsbreak system going in to repair DNA
5) during the process of repair is a looping out of the switch region -> removes piece of DNA, deleting IgM and only make IgG
Why are IgM low affinity?
Because AID doesn’t have an oppurtunity to make somatic hyper mutations
What are the symbols for IgG IgM, IgA, IgE?
IgG (y)
IgM (u)
IgA (o<)
IgE (E)
What three things do antibodies do?
1) Neutralise toxins
2) Aid phagocytosis of bacteria
3) Destroy bacteria
How do antibodies neutralise toxins?
1) Antibodies released and bind to bacterial toxin and neutralise
2) Toxin molecules bound by antibodies are digested by macrophage
3) Toxins and antibodies are digested by enzymes
How do antibodies aid phagocytosis of bacteria?
1) bacteria are present in extracellular space
2) Antibodies targeting bacteria are present in previously infected host
3) Antibodies bind antigens on bacteria
4) Antibodies and bacteria injested by macrophage and digested by enzxymes
How do antibodies directly destroy bacteria?
1) Bacteria present in extracellular space
2) Antibodies targeting bacteria are present in previously infected host
3) Antibodies bind to recognised sites on bacteria
4) A complement protein binds to the antibodies forming a complement protein complex on bacterial membrane
5) Complex forms a hole on bacterial membrane leading to bacteria losing osmotic control and being destroyed
What is tetanus caused by?
a neurotoxin produced by soil bacterium clostridium tetani under anaeobic conditions
What does the tetanus toxin do?
inhibits GABA or glyceine release (pre-synaptic activity) and in the absense of inhibitory neurotransmitters leads to unrestraineed excitation of neuroaxon leading to muscle spasm
How do antibodies protect against tetanus toxin? (vaccines)
1) Tetanus toxin treated with formaldehyde (so it retains it’s structure) which prevent activity to inactivate it, but allowing immune system 3D shape to bind to
2) injected with an adjuvant which induces a high affinity antibody response by anti-tetanus toxin specifc antibody producing B cell, to tetanus toxin
3) antibodies bind to tetanus protein and neutralise toxin
4) antibody prevents toxin having an effect but need high titre to protect against effects
What is the influenza virus?
rapidly evolving set of viruses which affects birds and mammals and is transmitted through aerosols
How do antibodies protect against influenza?
1) Virus haemagglutanin (HA) binds to epithelial surface on lung and mediates infection, allows virus to replicate
2) Antibodies mediate/neutralize HA prevent host cell infection
PROBLEM flu virus undergoes rapid recombination, new HA can dodge immune system, H1 strains nasty
How many people died of smallpox in the 20th centuary?
300-500 million deaths
